Pastorino L, Ikin A F, Lamprianou S, Vacaresse N, Revelli J P, Platt K, Paganetti P, Mathews P M, Harroch S, Buxbaum J D
Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA.
Mol Cell Neurosci. 2004 Apr;25(4):642-9. doi: 10.1016/j.mcn.2003.12.013.
BACE is an aspartyl protease that cleaves the amyloid precursor protein (APP) at the beta-secretase cleavage site and is involved in Alzheimer's disease. The aim of our study was to determine whether BACE affects the processing of the APP homolog APLP2. To this end, we developed BACE knockout mice with a targeted insertion of the gene for beta-galactosidase. BACE appeared to be exclusively expressed in neurons as determined by differential staining. BACE was expressed in specific areas in the cortex, hippocampus, cerebellum, pons, and spinal cord. APP processing was altered in the BACE knockouts with Abeta levels decreasing. The levels of APLP2 proteolytic products were decreased in BACE KO mice, but increased in BACE transgenic mice. Overexpression of BACE in cultured cells led to increased APLP2 processing. Our results strongly suggest that BACE is a neuronal protein that modulates the processing of both APP and APLP2.
β-分泌酶（BACE）是一种天冬氨酸蛋白酶，它在β-分泌酶切割位点切割淀粉样前体蛋白（APP），并与阿尔茨海默病有关。我们研究的目的是确定BACE是否影响APP同源物APLP2的加工过程。为此，我们培育了靶向插入β-半乳糖苷酶基因的BACE基因敲除小鼠。通过差异染色确定，BACE似乎仅在神经元中表达。BACE在大脑皮层、海马体、小脑、脑桥和脊髓的特定区域表达。在BACE基因敲除小鼠中，APP加工过程发生改变，β淀粉样蛋白（Aβ）水平降低。在BACE基因敲除小鼠中，APLP2蛋白水解产物水平降低，但在BACE转基因小鼠中升高。在培养细胞中过表达BACE导致APLP2加工增加。我们的结果强烈表明，BACE是一种神经元蛋白，可调节APP和APLP2的加工过程。
